rs202220375
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_201596.3(CACNB2):c.359G>A(p.Arg120Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120W) has been classified as Uncertain significance.
Frequency
Consequence
NM_201596.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.359G>A | p.Arg120Gln | missense_variant | 4/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.197G>A | p.Arg66Gln | missense_variant | 3/13 | ENST00000377329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.359G>A | p.Arg120Gln | missense_variant | 4/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.197G>A | p.Arg66Gln | missense_variant | 3/13 | 1 | NM_201590.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251322Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727224
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Aug 20, 2021 | - - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Brugada syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 66 of the CACNB2 protein (p.Arg66Gln). This variant is present in population databases (rs202220375, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 191431). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CACNB2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at